Pancreatic Cell News Volume 4.05 | Feb 12 2013

DIABETES

Incretin-Stimulated Interaction between β-Cell Kv1.5 and Kvβ2 Channel Proteins Involves Acetylation/Deacetylation by CBP/SirT1
The authors determined whether incretins modulate Kv1.5α/Kvβ2 interaction via post-translational modifications and the mechanisms involved. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) reduced apoptosis in INS-1 β-cells overexpressing Kv1.5, and RNAi-mediated knockdown of endogenous Kv1.5 attenuated apoptotic β-cell death. Further studies demonstrated that CREB binding protein (CBP)/Sirtuin deacetylase (SirT1) mediated acetylation/deacetylation and interaction between Kvβ2 and Kv1.5 in response to GIP/GLP-1. [Biochem J] Abstract

Hypoglycemia Reduces VEGF-A Production by Pancreatic Beta Cells as a Regulator of Beta Cell Mass
Scientists showed that secretion of vascular endothelial growth factor A (VEGF-A), but not VEGF-A gene transcription, in either cultured islets or purified pancreatic beta cells, was significantly reduced early on during low glucose conditions. [J Biol Chem] Abstract | Full Article

Glucocorticoid-Induced Suppression of β-Cell Proliferation Is Mediated by Mig6
Researchers hypothesized that dexamethasone impairs β-cell proliferation by increasing the expression of Mig6 and thereby decreasing downstream signaling of epidermal growth factor receptor. They found that Dex induced Mig6 and decreased [³H]thymidine incorporation, an index of cellular replication, in mouse, rat, and human islets. [Endocrinology] Abstract

Adipose Tissue-Derived Mesenchymal Stem Cells Efficiently Differentiate into Insulin-Producing Cells in Pancreatic Islet Microenvironment Both In Vitro and In Vivo
The differentiation of mesenchymal stem cells (MSCs) derived from rat tissues (adipose, rAT; bone marrow, rBM) were analyzed by in vitro and in vivo co-culture experiments. The insulin-producing capacities of islets transplanted under the renal kidney capsule with rAT- and rBM-MSCs were compared and the reduction of hyperglycemia symptoms in rat models was examined. [Cytotherapy] Abstract

Liver-Derived Systemic Factors Drive β Cell Hyperplasia in Insulin-Resistant States
To test the hypothesis that crosstalk between the liver and pancreatic islets modulates β cell growth in response to insulin resistance, investigators used the liver-specific insulin receptor knockout mouse, a unique model that exhibits dramatic islet hyperplasia. [Cell Rep] Full Article | Graphical Abstract

PANCREATIC CANCER

Enhancer of Zeste Homolog 2 Silences miR-218 in Human Pancreatic Ductal Adenocarcinoma Cells by Inducing Formation of Heterochromatin
The authors identified microRNAs (miRs) that are regulated by enhancer of zeste homolog 2 (EZH2) and studied their functions in pancreatic ductal adenocarcinoma (PDAC) cells. They performed miR profile analysis of PDAC cells incubated with EZH2 inhibitor DZnep, and pancreatic ductal epithelial cells that overexpressed EZH2. [Gastroenterology] Abstract

Targeting Gemcitabine Containing Liposomes to CD44 Expressing Pancreatic Adenocarcinoma Cells Causes an Increase in the Antitumoral Activity
Scientists investigated the cellular delivery ability and both in vitro and in vivo anti-tumoral activity of liposomes conjugated with two different low molecular weight hyaluronic acid (HA), the primary ligand of CD44, and containing a lipophilic gemcitabine pro-drug. By confocal microscopy and flow cytometry analyses, they demonstrated that the cellular uptake into a highly CD44-expressing pancreatic adenocarcinoma cell line is higher with HA-conjugated than non-conjugated liposomes. [Biochim Biophys Acta] Abstract

Reduction in ATP Levels Triggers Immunoproteasome Activation by the 11S (PA28) Regulator during Early Antiviral Response Mediated by IFNβ in Mouse Pancreatic β-Cells
Of special interest to immunoproteasome activation in β-cells are the effects of IFNβ, a type I IFN secreted by virus-infected cells and implicated in type I diabetes onset, compared to IFNγ, the classic immunoproteasome inducer secreted by cells of the immune system. By qPCR analysis, researchers showed that mouse insulinoma MIN6 cells and mouse islets accumulate the immune proteolytic β1i, β2i and β5i, and 11S mRNAs upon exposure to IFNβ or IFNγ. [PLoS One] Full Article

Microenvironment Generated during EGFR Targeted Killing of Pancreatic Tumor Cells by ATC Inhibits Myeloid-Derived Suppressor Cells through COX2 and PGE2 Dependent Pathway
Researchers investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of myeloid-derived suppressor cells (MDSCs) in the presence or absence of Th1 microenvironment. They used 3D co-culture model of peripheral blood mononuclear cells with pancreatic cancer cells MiaPaCa-2 and gemcitabine resistant MiaPaCa-GR cells to generate MDSC in the presence or absence of Th1 cytokines and EGFRBi armed ATC. [J Transl Med] Abstract | Full Article

REVIEWS

Prospects on Human Embryonic Stem Cell-Derived Pancreatic Progenitor Expansion
Scientists discuss present approaches, as well as future alternatives, in the fields of basic and clinic research on β cell differentiation, derivation and transplantation. [Cell Res] Full Article

Exploiting Inflammation for Therapeutic Gain in Pancreatic Cancer
This review explores the pathways known to modulate inflammation at different stages of tumor development, drawing conclusions on their potential as therapeutic targets in pancreatic ductal adenocarcinoma. [Br J Cancer] Full Article

From Pancreatic Islet Formation to Beta-Cell Regeneration
The authors describe briefly the genetic program underlying mouse pancreas development and present new insights regarding β-cell regeneration. [Diabetes Res Clin Pract] Abstract

Levine Cancer Institute, UNC Charlotte Announce Innovative Pancreatic Cancer Research Partnership
Carolina HealthCare System’s Levine Cancer Institute and University of North Carolina (UNC) Charlotte will enter into a joint project to advance translational and clinical research in the field of pancreatic cancer. The collaborative effort aims to foster more working relationships between physicians and scientists at both institutions by offering funding for innovative research ideas, submitted to and reviewed by a committee of their peers. [The University of North Carolina at Charlotte] Press Release

Novo Nordisk Receives Complete Response Letter in the US for Tresiba^® and Ryzodeg^®
Novo Nordisk announced that it received a Complete Response Letter from the US Food and Drug Administration (FDA) regarding the New Drug Applications for Tresiba^® (insulin degludec) and Ryzodeg^® (insulin degludec/insulin aspart). A Complete Response Letter is issued by the FDA, when the agency determines that an application cannot be approved in its current form. [Novo Nordisk A/S] Press Release

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NEW StemCONN 2013: Realizing the Promise 
April 3, 2013
New Haven, United States

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Postdoctoral Position – Diabetes Research (Lund University)

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Postdoctoral Position – Diabetes Research (Sanofi-Aventis Deutschland GmbH)

Postdoctoral Position – Pancreas Development (INSERM)

Postdoc Position – Beta Cell Signaling (The University of Southern Denmark)

Postdoctoral Position (Skirball Institute / NYU Medical Center)

PhD Studentship – Developmental Genes in Adult Pancreas Homeostasis & Energy Metabolism (Helmholtz Zentrum München)

Research Position – Diabetes Research (Johns Hopkins University)

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